Treatment Patterns and Adverse Event-Related Hospitalization Among Patients with Epidermal Growth Factor Receptor (EGFR)-Mutated Metastatic Non-small Cell Lung Cancer After Treatment with EGFR Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy Regimens.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKIs) are established first-line treatments among patients with metastatic non-small cell lung cancer harboring EGFR-sensitizing mutations. Upon EGFR TKI resistance, there are scant data supporting a standard of care in subsequent lines of therapy. OBJECTIVE: We aimed to characterize real-world treatment patterns and adverse events associated with hospitalization in later lines of therapy. METHODS: This retrospective analysis of administrative claims included adults with metastatic non-small cell lung cancer who initiated a next line of therapy (index line of therapy) following EGFR TKI and platinum-based chemotherapy discontinuation on/after 1 November, 2015. Treatment regimens and adverse event rates during the index line of therapy were described. RESULTS: Among 195 eligible patients (median age: 59 years; female: 60%), the five most common index line of therapy regimens were immune checkpoint inhibitor monotherapy (29%), EGFR TKI monotherapy (21%), platinum-based chemotherapy (19%), non-platinum-chemotherapy (13%), and EGFR TKI combinations (9%). The overall median (95% confidence interval) time to discontinuation of the index line of therapy was 2.8 (2.1-3.2) months. Common adverse events associated with hospitalizations included infection/sepsis, pneumonia/pneumonitis, and anemia (2.9, 2.8, and 2.0 per 100 person-months, respectively). CONCLUSIONS: Among EGFR TKI-resistant patients who discontinued platinum-based chemotherapy, the duration of the next line of therapy was short, treatment was highly variable, and re-treatment with EGFR TKIs and platinum-based regimens was common, suggesting a lack of standard of care in later lines. Adverse event rates associated with hospitalization were high, especially among platinum-treated patients. These results underscore the unmet need for new therapies in a later line of treatment to reduce the clinical burden among patients in this population.

Real-World Treatment Patterns and Outcomes Following First-Line Pertuzumab and Trastuzumab Among Patients with HER2+ Metastatic Breast Cancer.

INTRODUCTION: Many patients with human epidermal growth factor receptor-2-positive metastatic breast cancer (HER2+ mBC) require subsequent lines of therapy (LOTs) after being treated with pertuzumab and trastuzumab-based regimens in the first line (1L). Although the efficacy of the second-line (2L) therapies has been demonstrated in clinical trials, the real-world effectiveness of these treatments is understudied. This retrospective cohort study assessed the real-world treatment patterns and outcomes for patients with HER2+ mBC following 1L therapy with pertuzumab and trastuzumab-based regimens in the United States (US) during 2015-2019. METHODS: Adults with HER2+ mBC in the US who initiated 1L pertuzumab and trastuzumab-based regimens between 01/01/2015 and 09/30/2019 and had ≥ 60 days of follow-up after 1L initiation were identified from the IQVIA Oncology Electronic Medical Records database. The regimens utilized in 2L following 1L pertuzumab and trastuzumab-based regimens were described. Median treatment duration and time to treatment failure were reported for 2L based on Kaplan-Meier analyses. RESULTS: Of the 710 eligible patients who received pertuzumab and trastuzumab-based regimens in 1L (median age: 57.0 years [interquartile range: 48.0-65.0]; median follow-up: 20.3 months; median 1L duration: 15.3 months), 222 (31.3%) initiated 2L. The most common regimens in 2L were ado-trastuzumab emtansine (T-DM1)-based regimens (n = 159 [71.6%]), followed by lapatinib-based (n = 21 [9.5%]) and neratinib-based (n = 18 [8.1%]) regimens. The median treatment duration and time to treatment failure were 5.9 (95% CI: 5.0, 8.7) and 8.6 (7.3, 11.5) months, respectively, among patients initiating 2L, and 5.7 (4.7, 7.8) and 7.9 (6.5, 10.0) months among those receiving 2L T-DM1. CONCLUSIONS: Most patients with HER2+ mBC requiring additional treatments after 1L pertuzumab and trastuzumab-based regimens utilized T-DM1 in 2L during 2015-2019. The short median treatment duration and time to treatment failure highlight an unmet need that can potentially be fulfilled by recently approved treatment options.

Fracture risk in women with osteoporosis initiated on gastro-resistant risedronate versus immediate release risedronate or alendronate: a claims data analysis in the USA.

The study results indicate that women with osteoporosis initiated on gastro-resistant risedronate have a lower risk of fracture than those initiated on immediate release risedronate or alendronate. A large proportion of women discontinued all oral bisphosphonate therapies within 1 year of treatment start. PURPOSE: Using a US claims database (2009-2019), we compared risk of fractures between women with osteoporosis initiated on gastro-resistant (GR) risedronate and those initiated on (a) immediate release (IR) risedronate or (b) immediate release alendronate. METHODS: Women aged ≥ 60 years with osteoporosis who had ≥ 2 oral bisphosphonate prescription fills were followed for ≥ 1 year after the first observed bisphosphonates dispensing (index date). Fracture risk was compared between the GR risedronate and IR risedronate/alendronate cohorts using adjusted incidence rate ratios (aIRRs), both overall and in subgroups with high fracture risk due to older age or comorbidity/medications. Site-specific fractures were identified based on diagnosis codes recorded on medical claims using a claims-based algorithm. Persistence on bisphosphonate therapy was evaluated for all groups. RESULTS: aIRRs generally indicated lower fracture risk for GR risedronate than IR risedronate and alendronate. When comparing GR risedronate to IR risedronate, statistically significant aIRRs (p < 0.05) were observed for pelvic fractures in the full cohorts (aIRRs = 0.37), for any fracture and pelvic fractures among women aged ≥ 65 years (aIRRs = 0.63 and 0.41), for any fracture and pelvic fractures among women aged ≥ 70 years (aIRRs = 0.69 and 0.24), and for pelvic fracture among high-risk women due to comorbidity/medications (aIRR = 0.34). When comparing GR risedronate to alendronate, statistically significant aIRRs were observed for pelvic fractures in the full cohorts (aIRR = 0.54), for any fracture and wrist/arm fractures among women aged ≥ 65 years (aIRRs = 0.73 and 0.63), and for any fracture, pelvic, and wrist/arm fractures among women aged ≥ 70 years (aIRRs = 0.72, 0.36, and 0.58). In all cohorts, ~ 40% completely discontinued oral bisphosphonates within 1 year. CONCLUSIONS: Discontinuation rates of oral bisphosphonate therapy were high. However, women initiated on GR risedronate had a significantly lower risk of fracture for several skeletal sites than women initiated on IR risedronate/alendronate, particularly those aged ≥ 70 years.

Health-care resource use and costs associated with diabetic and idiopathic gastroparesis: A claims analysis of the first 3 years following the diagnosis of gastroparesis.

BACKGROUND: Due to limited treatment options, many patients with diabetic gastroparesis (DG) or idiopathic gastroparesis (IG) experience inadequate symptom control resulting in increased health-care resource utilization (HRU) and associated costs. We compared all-cause HRU and health-care costs over the 3 years after patients' first gastroparesis diagnosis with that of matched controls without gastroparesis. METHODS: Newly diagnosed adults with DG or IG were identified in Optum's de-identified Clinformatics® Data Mart Database (Q1-2007 to Q1-2019). Patients with DG/IG were matched 1:1 to controls using a mixed approach of exact matching and propensity score matching. The index date was the first gastroparesis diagnosis for cases or randomly selected for controls. All-cause HRU and direct health-care costs per person-year (PPY) were compared between DG/IG cases and controls in Years 1-3 post-index. KEY RESULTS: Demographics and comorbidities were balanced between patients with gastroparesis (n = 18,015 [DG]; n = 14,305 [IG]) and controls. In each of the Years 1-3 post-index, patients with DG or IG had significantly higher annual HRU and costs versus controls (mean total cost differences PPY: DG Year 1 $34,885, Year 2 $28,071, Year 3 $25,606; IG Year 1 $23,176, Year 2 $16,627, Year 3 $14,396) (all p < 0.05). Across all 3 years, DG/IG cohorts had approximately twice the costs of controls. HRU and costs were highest in Year 1 post-index for both DG and IG. CONCLUSIONS & INFERENCES: The economic burden of gastroparesis remains high several years after diagnosis, emphasizing the need for chronic treatment to effectively manage symptoms and consequently reduce the burden of this disorder.

Reasons for Initiating Canakinumab among Patients with Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease in the U.S. Real-World Settings.

INTRODUCTION: The aim of this study was to understand the reasons for canakinumab initiation among patients with Still's disease, including systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still's disease (AOSD), in US clinical practice. METHODS: Physicians retrospectively reviewed the medical charts of patients with Still's disease (regardless of age at symptom onset) who were prescribed canakinumab from 2016 to 2018. Patients aged < 16 years at symptom onset were classified as having SJIA and those aged ≥ 16 years at symptom onset (calculated from case-record forms) were classified as having AOSD. Patient treatment history and physician reasons for canakinumab initiation were analyzed. Overall results were presented as SJIA/AOSD. Sensitivity analyses were performed for the robustness of the results. RESULTS: Forty-three physicians in the USA (rheumatologists/dermatologists/immunologists/allergists: 51.2/27.9/11.6/9.3%; subspecialty in adults/pediatrics: 67.4/32.6%) abstracted information for 72 patients with SJIA/AOSD (SJIA/AOSD/age unknown at symptom onset: 75.0/18.1/6.9%; mean age 19.4 years; children 61.1%; females 56.9%). Most patients (90.3%) received treatment directly preceding canakinumab initiation (etanercept 27.7%; anakinra 18.5%; adalimumab 16.9%); the respective treatment was discontinued due to lack of efficacy/effectiveness (43.1%) and availability of a new treatment (27.8%). Most common reasons for canakinumab initiation were physician perceived/experienced efficacy/effectiveness of canakinumab (77.8%; children/adults: 81.8/71.4%), lack-of-response to previous treatment (45.8%; children/adults: 36.4/60.7%), convenient administration/dosing (26.4%; children/adults: 29.5/21.4%) and ability to discontinue/spare steroids (25.0%; children/adults: 20.5/32.1%). The sensitivity analysis provided similar results. CONCLUSIONS: In US clinical practice, physician perceived/experienced efficacy/effectiveness of canakinumab and lack-of-response to previous treatment were the primary reasons for canakinumab initiation among patients with SJIA/AOSD. Physician perceived/experienced efficacy/effectiveness and convenient administration/dosing of canakinumab were the most common reasons for canakinumab initiation among children, whereas lack-of-response to previous treatment and ability to discontinue/spare steroids being the most frequent reasons among adults.

Reasons for canakinumab initiation among patients with periodic fever syndromes: a retrospective medical chart review from the United States.

BACKGROUND: Although canakinumab has demonstrated efficacy in multiple trials in patients with periodic fever syndromes (PFS), the evidence on initiation of canakinumab among PFS patients in real world setting is not well understood. We aimed to characterize the reasons for canakinumab initiation among patients with PFS, specifically, cryopyrin-associated periodic syndrome (CAPS), hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF). METHODS: Physicians retrospectively reviewed the medical charts of PFS patients prescribed canakinumab between 2016 and 2018. Information collected included patient clinical characteristics, reasons for previous treatment discontinuation and canakinumab initiation. The results were summarized for overall patients, and by children (< 18 years) and adults and by subtype of PFS. RESULTS: Fifty-eight physicians in the US (rheumatologists, 44.8 %; allergists/immunologists, 29.3 %; dermatologists, 25.9 %) abstracted information for 147 patients (children, 46.3 %; males, 57.1 %; CAPS, 36.7 %; TRAPS, 26.5 %; FMF, 26.5 %; HIDS/MKD, 6.8 %; Mixed, 3.4 %). Overall, most patients (90.5 %) received treatment directly preceding canakinumab (NSAIDs, 27.8 % [40.0 % in HIDS/MKD]; anakinra, 24.1 % [32.7 % in CAPS]; colchicine, 21.8 % [35.9 % in FMF]), which were discontinued due to lack of efficacy/effectiveness (39.5 %) and availability of a new treatment (36.1 %). The common reasons for canakinumab initiation were physician perceived efficacy/effectiveness (81.0 %; children, 75.0 %; adults, 86.1 %), lack of response to previous treatment (40.8 %; children, 38.2 %; adults, 43.0 %) and favorable safety profile/tolerability (40.1 %; children, 42.6 %; adults, 38.0 %). Within subtypes, efficacy/effectiveness was the most stated reason for canakinumab initiation in HIDS/MKD (90.9 %), lack of response to previous treatment in FMF (52.4 %) and convenience of administration/dosing in CAPS (27.1 %). CONCLUSIONS: This study provided insights into how canakinumab is initiated in US clinical practice among PFS patients, with physician perceived efficacy/effectiveness of canakinumab, lack of response to previous treatment and favorable safety profile/tolerability of canakinumab being the dominant reasons for canakinumab initiation in all patients and in children and adults and PFS subtypes. Notably, the favorable safety profile/tolerability of canakinumab was more often the reason for initiation among children versus adults.

Beyond Frontline Therapy with Abiraterone and Enzalutamide in Metastatic Castration-Resistant Prostate Cancer: A Real-World US Study.

BACKGROUND: Real-world evidence suggest that next generation hormonal agents (NHAs) abiraterone and enzalutamide were preferred as first-line (1L) therapies for metastatic castration-resistant prostate cancer (mCRPC) in the United States (US) pre-2020, with chemotherapies, particularly docetaxel, being preferred in subsequent lines (2L+). This real-world study described patient characteristics, treatment patterns, time on treatment (ToT) and overall survival (OS) among patients with mCRPC treated with 2L and 3L docetaxel post-NHAs in the mCRPC setting. METHODS: Adults with confirmed adenocarcinoma mCRPC diagnosis and ≥1 month of follow-up post-diagnosis were selected from a US electronic health record-derived oncology de-identified database (01/2013-03/2019). Based on the observed line of therapy sequences post-mCRPC diagnosis, patients who received NHA therapy in 1L and docetaxel therapy in 2L were included in the 2L docetaxel cohort, and patients who received NHA therapy in both 1L and 2L and docetaxel therapy in 3L were included in the 3L docetaxel cohort. ToT and OS were evaluated using Kaplan-Meier analysis. RESULTS: Among 5,213 patients with mCRPC, 278 and 166 were included in the 2L and the 3L docetaxel cohorts, respectively (median age: 73 years for both cohorts). ADT was the most used class of medication pre-mCRPC (>75%). For the 2L cohort, the most common sequence post-mCRPC was 1L abiraterone â†’ 2L docetaxel (52.5%), while the median ToT and OS post-2L start were 4.1 and 10.5 months, respectively; for the 3L cohort, the most common sequence post-mCRPC was 1L abiraterone â†’ 2L enzalutamide â†’ 3L docetaxel (67.5%), while the median ToT and OS post-3L start were 3.8 and 8.7 months, respectively. CONCLUSIONS: This real-world study provides novel data on patients treated with docetaxel post-NHAs in a mCRPC setting and highlights the critical unmet need for developing more effective treatment options in this population.

Classification, Prediction, and Concordance of Cognitive and Functional Progression in Patients with Mild Cognitive Impairment in the United States: A Latent Class Analysis.

BACKGROUND: Progression trajectories of patients with mild cognitive impairment (MCI) are currently not well understood. OBJECTIVE: To classify patients with incident MCI into different latent classes of progression and identify predictors of progression class. METHODS: Participants with incident MCI were identified from the US National Alzheimer's Coordinating Center Uniform Data Set (09/2005-02/2019). Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and Mini-Mental State Examination (MMSE) score longitudinal trajectories from MCI diagnosis were fitted using growth mixture models. Predictors of progression class were identified using multivariate multinomial logistic regression models; odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS: In total, 21%, 22%, and 57% of participants (N = 830) experienced fast, slow, and no progression on CDR-SB, respectively; for FAQ, these figures were 14%, 23%, and 64%, respectively. CDR-SB and FAQ class membership was concordant for most participants (77%). Older age (≥86 versus≤70 years, OR [95% CI] = 5.26 [1.78-15.54]), one copy of APOE ɛ4 (1.94 [1.08-3.47]), higher baseline CDR-SB (2.46 [1.56-3.88]), lower baseline MMSE (0.85 [0.75-0.97]), and higher baseline FAQ (1.13 [1.02-1.26]) scores were significant predictors of fast progression versus no progression based on CDR-SB (all p < 0.05). Predictors of FAQ class membership were largely similar. CONCLUSION: Approximately a third of participants experienced progression based on CDR-SB or FAQ during the  4-year follow-up period. CDR-SB and FAQ class assignment were concordant for the vast majority of participants. Identified predictors may help the selection of patients at higher risk of progression in future trials.

Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors.

INTRODUCTION: Therapeutic options for metastatic castration-resistant prostate cancer (mCRPC) patients are continuously advancing. We described mCRPC treatment patterns in the US from 2013 to 2019. METHODS: Patients with a confirmed mCRPC diagnosis and adenocarcinoma histology were included in the US Flatiron Health Electronic Health Record-derived de-identified database. Treatment patterns [including treatment per lines of therapies (LOTs), LOT sequences, and time on treatment] and overall survival (OS) have been described in mCRPC settings. RESULTS: Of 5213 patients (mean age: 72.6 years), 4374 (83.9%) were treated with ≥ 1 LOT post-mCRPC diagnosis (among those with ≥ 1 LOT, 55.3%, 29.5%, 14.7%, and 6.7% had ≥ 2, 3, 4, and 5 LOTs, respectively). In first line (1L), the main treatment class was next-generation hormonal agents (NHA; 62.5% of patients with ≥ 1 LOT), while the shortest and longest time on 1L were observed for chemotherapy (median 2.8 months) and NHA (median 5.1 months), respectively. The most common LOT sequences were NHA â†’ NHA (29.4% of patients with ≥ 2 LOTs) and NHA â†’ NHA â†’ chemotherapy (16.7% of patients with ≥ 3 LOTs). In Kaplan-Meier analyses, the median OS was 19.4, 14.6, and 11.1 months post-1L, 2L, and 3L start, respectively. Patients who moved rapidly through LOTs had an increased risk of death. CONCLUSIONS: NHA were widely used as 1L therapy in mCRPC patients from 2013 to 2019, but time on 1L NHA treatment was on average < 6 months. While NHA â†’ NHA was the most observed 1L â†’ 2L LOT sequence, a plethora of other LOT sequences were observed. OS was poor, highlighting an unmet need for life-prolonging treatments.

Real-world genetic testing patterns in metastatic castration-resistant prostate cancer.

Aim: To assess the patterns of genetic testing for homologous recombination repair mutations in patients with metastatic castration-resistant prostate cancer (mCRPC) pre-PARP inhibitors approval. Patients & methods: mCRPC patients were selected in an oncology electronic medical records database. Patterns and predictors of testing for ATM, BRCA1/2, CDK12, PALB2 and FANCA gene alterations were assessed. Results: Of 5213 mCRPC patients, 674 (13%) had a documented genetic test. The number of tested patients increased from 1 in 2013 to 313 in 2018 (out of 3161 and 3010 clinically active patients, respectively). Receiving care in an academic oncology center (versus a community-based center) strongly predicted genetic testing (hazard ratio = 2.41). Conclusion: The use of and access to genetic testing pre-PARP inhibitor approval was suboptimal.

Lay abstract In 2017, US guidelines recommended the use of genetic testing in patients with metastatic castration-resistant prostate cancer (mCRPC). While the initial goal of genetic testing was to guide referral to genetic counselling and clinical trial enrollment, it is now also used to identify patients who could benefit from new drugs that target specific molecular defects. Using medical record data of US patients with mCRPC, we found that the rates of genetic testing and the breadth of molecular defects tested were suboptimal from 2013 to 2019. We also found lower rates of genetic testing in patients treated in community-based centers compared with those treated in academic oncology centers. These results underscore the importance of increasing the take up rate of genetic testing in patients with mCRPC to help guide treatment decisions.